Shape memory materials are defined by their capacity to recover a predetermined shape after significant mechanical deformation (K. Otsuka and C. M. Wayman, “Shape Memory Materials” New York: Cambridge University Press, 1998). The shape memory effect can be initiated by a number of stimuli including by a change in temperature and has been observed in metals, ceramics, and polymers. From a macroscopic point of view, the shape memory effect in polymers differs from ceramics and metals due to the lower stresses and larger recoverable strains achieved in polymers.
The basic thermomechanical response of shape memory polymer (SMP) materials is defined by four critical temperatures. The glass transition temperature, Tg, is typically represented by a transition in modulus-temperature space and can be used as a reference point to normalize temperature for some SMP systems. SMPs offer the ability to vary Tg over a temperature range of several hundred degrees by control of chemistry or structure. The predeformation temperature, Td, is the temperature at which the polymer is deformed into its temporary shape. Depending on the required stress and strain level, the initial deformation Td can occur above or below Tg (Y. Liu, K. Gall, M. L. Dunn, and P. McCluskey, “Thermomechanical Recovery Couplings of Shape Memory Polymers in Flexure.” Smart Materials & Structures, vol. 12, pp. 947-954, 2003). The storage temperature, Ts, represents the temperature in which no shape recovery occurs and is equal to or is below Td. The storage temperature Ts is less than the glass transition temperature Tg. At the recovery temperature, Tr, the shape memory effect is activated, which causes the material to substantially recover its original shape. Tr is above Ts and is typically in the vicinity of Tg. Recovery can be accomplished isothermally by heating the material to a fixed Tr and then holding, or by continued heating up to and past Tr. From a macroscopic viewpoint, a polymer will demonstrate a useful shape memory effect if it possesses a distinct and significant glass transition (B. Sillion, “Shape memory polymers,” Act. Chimique., vol. 3, pp. 182-188, 2002), a modulus-temperature plateau in the rubbery state (C. D. Liu, S. B. Chun, P. T. Mather, L. Zheng, E. H. Haley, and E. B. Coughlin, “Chemically cross-linked polycyclooctene: Synthesis, characterization, and shape memory behavior.” Macromolecules. vol. 35, no. 27, pp. 9868-9874, 2002), and a large difference between the maximum achievable strain, εmax, during deformation and permanent plastic strain after recovery, εp (F. Li, R. C. Larock, “New Soybean Oil-Styrene-Divinylbenzene Thermosetting Copolymers. V. Shape memory effect.” J. App. Pol. Sci., vol. 84, pp. 1533-1543, 2002). The difference εmax−εp is defined as the recoverable strain, εrecover, while the recovery ratio is defined as εrecover/εmax.
The microscopic mechanism responsible for shape memory in polymers depends on both chemistry and structure (T. Takahashi, N. Hayashi, and S. Hayashi, “Structure and properties of shape memory polyurethane block copolymers.” J. App. Pol. Sci., vol. 60, pp. 1061-1069, 1996; J. R. Lin and L. W. Chen, “Study on Shape-Memory Behavior of Polyether-Based Polyurethanes. II. Influence of the Hard-Segment Content.” J. App. Pol. Sci., vol. 69, pp. 1563-1574, 1998; J. R. Lin and L. W. Chen, “Study on Shape-Memory Behavior of Polyether-Based Polyurethanes. I. Influence of soft-segment molecular weight.” J. App. Pol. Sci., vol 69, pp. 1575-1586, 1998; F. Li, W. Zhu, X. Zhang, C. Zhao, and M. Xu, “Shape memory effect of ethylene-vinyl acetate copolymers.” J. App. Poly. Sci., vol. 71, pp. 1063-1070, 1999; H. G. Jeon, P. T. Mather, and T. S. Haddad, “Shape memory and nanostructure in poly(norbornyl-POSS) copolymers.” Polym. Int., vol. 49, pp. 453-457, 2000; H. M. Jeong, S. Y. Lee, and B. K. Kim, “Shape memory polyurethane containing amorphous reversible phase.” J. Mat. Sci., vol. 35, pp. 1579-1583, 2000; A. Lendlein, A. M. Schmidt, and R. Langer, “AB-polymer networks based on oligo(epsilon-caprolactone) segments showing shape-memory properties.” Proc. Nat. Acad. Sci., vol. 98, no. 3, pp. 842-847, 2001; G. Zhu, G. Liang, Q. Xu, and Q. Yu, “Shape-memory effects of radiation crosslinked poly(epsilon-caprolactone).” J. App. Poly. Sci., vol. 90, pp. 1589-1595, 2003). One driving force for shape recovery in polymers is the low conformational entropy state created and subsequently frozen during the thermomechanical cycle (C. D. Liu, S. B. Chun, P. T. Mather, L. Zheng, E. H. Haley, and E. B. Coughlin, “Chemically cross-linked polycyclooctene: Synthesis, characterization, and shape memory behavior.” Macromolecules. Vol. 35, no. 27, pp. 9868-9874, 2002). If the polymer is deformed into its temporary shape at a temperature below Tg, or at a temperature where some of the hard polymer regions are below Tg, then internal energy restoring forces will also contribute to shape recovery. In either case, to achieve shape memory properties, the polymer must have some degree of chemical crosslinking to form a “memorable” network or must contain a finite fraction of hard regions serving as physical crosslinks.
SMPs are processed in a manner that is termed programming, whereby the polymer is deformed and set into a temporary shape. (A. Lendlein, S. Kelch, “Shape Memory Polymer,” Advanced Chemie, International Edition, 41, pp. 1973-2208, 2002.) When exposed to an appropriate stimulus, the SMP substantially reverts back to its permanent shape from the temporary shape. The stimulus may be, for example, temperature, magnetic field, water, or light, depending on the initial monomer systems.
For SMPs used in medical devices, wherein temperature is the chosen stimulus, an external heat source may be used to provide discretionary control of the shape recovery by the physician, or the body's core temperature may be utilized to stimulate the shape recovery upon entry or placement within the body from the environmental temperature, which may be room temperature. (Small W, et al. “Biomedical applications of thermally activated shape memory polymers” Journal of Materials Chemistry, Vol 20, pp 3356-3366, 2010.)
For implantable medical devices, the life expectancy of the device can be defined by the duration that it must maintain its mechanical properties and functionality in the body. For biodegradable devices, this life expectancy is intentionally short, providing a mechanism for the material and device to degrade over time and be absorbed by the body's metabolic processes. For non-biodegradable devices, referred to as biodurable devices, or devices exhibiting biodurability, they are not intended to degrade and they must maintain their material properties and functionality for longer periods, possibly for the life the patient.
For medical devices used within the body, either permanent implants or instrumentation used for diagnostic or therapeutic purposes, the ability to visualize the device using typical clinical imaging modalities, e.g. X-ray, Fluoroscopy, CT Scan, and MRI is typically a requirement for clinical use. Devices intended to be imaged by X-ray and Fluoroscopy, typically contain either metals or metal byproducts to induce radiopacity. Radiopacity refers to the relative inability of electromagnetism, particularly X-rays, to pass through dense materials, which are described as ‘radiopaque’ appearing opaque/white in a radiographic image. A more radiopaque material appears brighter, whiter, on the image. (Novelline, Robert. Squire's Fundamentals of Radiology. Harvard University Press. 5th edition. 1997.) Given the complexity of the content within an X-ray or Fluoroscopic image, clinicians are sensitive to the quality of the image regarding the brightness or signal strength of the material in the image. The two main factors that contribute to radiopacity brightness, or signal strength of a material are density and atomic number. Polymer based medical devices requiring radiopacity typically utilize a polymer blend that incorporates a small amount, by weight percent, of a heavy atom, radiopaque filler such as Titanium Dioxide (TiO2), or Barium Sulfate (BaSO4). The device's ability to be visualized on fluoroscopy is dependent upon the amount, or density, of the filler mixed into the material, which is typically limited to a small quantity as the filler can detrimentally affect the base polymer's material properties. Meanwhile, medical device imaging companies have developed standardized liquid contrast media to be intermittently used by physicians to highlight vascular structures, etc. during X-ray or Fluoroscopy when filled with this contrast media. This media commonly contains a heavy atom fluid, such as iodine, to induce radiopacity.
Iodine-incorporating monomers were reported by Mosner et al., who reported 3 different triiodinated aromatic monomers, which differed in the degree to which they could be homopolymerized or required copolymerization in order to be incorporated. (Moszner et al. “Synthesis and polymerization of hydrophobic iodine-containing methacrylates” Die Angewandte Makromolekulare Chemie 224 (1995) 115-123) Iodinating monomers was also pursued by Koole et al. in the Netherlands, as published from 1994-1996 with a range of monoiodinated to triiodinated aromatic monomers (Koole et al. “Studies on a new radiopaque polymeric biomaterial,” Biomaterials 1994 November; 15(14):1122-8. Koole et al. “A versatile three-iodine molecular building block leading to new radiopaque polymeric biomaterials,” J Biomed Mater Res, 1996 November; 32(3):459-66). This included biocompatibility results of a 2-year implantation study in rats of monoiodinated aromatic methacrylate copolymer systems. (Koole et al. “Stability of radiopaque iodine-containing biomaterials,” Biomaterials 2002 February; 23(3):881-6) They are also discussed by Koole in U.S. Pat. No. 6,040,408, filed initially as a European patent application in August, 1994, which limits its claims to aromatic monomers containing no more than two covalently bonded iodine groups. (U.S. Pat. No. 6,040,408, “Radiopaque Polymers and Methods for Preparation Thereof,” Koole, 21 Mar. 2000). Also, US Patent Application 20060024266 by Brandom et al. claimed polyiodinated aromatic monomers in shape memory polymers, emphasizing the use of crystallizable polymer side-groups (US Patent Application 20060024266, “Side-chain crystallizable polymers for medical applications, Brandom et al., 5 Jul. 2005).
WO 2012/019145 and U.S. Ser. No. 61/762,416 describe shape memory materials having crosslinked radiopaque iodinated aromatic monomers. Both of these applications are hereby incorporated by reference in their entirety.
Materials, including shape memory polymers, having useful properties including enhanced radiopacity are desired. As a specific example, shape memory materials with enhanced radiopacity that is useful for imaging biomaterial implants of small size and thickness while retaining critical performance properties, including rapid shape retention upon emergence from a deployment catheter and mechanical durability to prevent fracture and release of fragments, is desired.